Functional characterization of receptor-type protein tyrosine phosphatase CD148 (HPTP eta/DEP-1) in Fc gamma receptor IIa signal transduction of human neutrophils.
Activation of the 40-kDa low-affinity receptor for IgG (Fc gammaRIIa, CD32) leads to tyrosine phosphorylation, increase of cytosolic free calcium concentration ([Ca2+]i), and production of superoxide anions (O2-) in neutrophils (PMN). It has been established that protein tyrosine kinases (PTK) and phosphatases (PTP) are essential for the regulation of intracellular signaling. CD45 is a type I receptor-type protein tyrosine phosphatase (RPTP) with two PTP domains. Recently it has been demonstrated that co-cross-linking of CD45 modulates the signal transduction pathway of Fc gammaRIIa in PMN. In contrast, the functional characteristics of CD148 (HPTP eta/DEP-1), a new RPTP with only one PTP domain, is unknown. CD148 is expressed on PMN in slightly lower density than CD45, and in higher density than on lymphocytes. [Ca2+]i measured with fluo-3-loaded PMN by flow cytometry and O2- production determined by lucigenin-dependent chemiluminescence were inhibited by co-cross-linking of CD45 with Fc gammaRIIa in comparison to isotype control monoclonal antibody (mAb). In contrast, pre-incubation with CD148 mAb 143-41 abolished O2- generation, but did not inhibit [Ca2+]i rise. In summary, both clustered human RPTP, CD45 and CD148, inhibit Fc gammaRIIa-induced O2- production in PMN, but they differ in regulation of [Ca2+]i. Therefore, it is suggested that co-cross-linking of Fc gammaRII with CD45 and CD148 leads to dephosphorylation of different substrates. These distinct functional capacities may be important for differential regulation of Fc gammaR signaling by currently unknown ligands.
Hundt
M
M
Medizinische Hochschule Hannover, Abteilung Klinische Immunologie, Germany. Hundt.Matthias@MH-Hannover.de
Schmidt
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D006801:Humans; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D017452:Receptors, IgG / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D017452:Receptors, IgG; C486288:PTPRJ protein, human; D017027:Protein Tyrosine Phosphatases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3